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BACKGROUND: Calcific aortic stenosis (CAS) is more prevalent, occurs earlier, progresses faster and has worse outcomes in patients with chronic kidney disease (CKD). The uremic toxin indoxyl sulfate (IS) is powerful predictor of cardiovascular mortality in these patients and a strong promoter of ectopic calcification whose role in CAS remains poorly studied. The objective of this study was to evaluate whether IS influences the mineralization of primary human valvular interstitial cells (hVICs) from the aortic valve. METHODS: Primary hVICs were exposed to increasing concentrations of IS in osteogenic medium (OM). The hVICs' osteogenic transition was monitored by qRT-PCRs for BMP2 and RUNX2 mRNA. Cell mineralization was assayed using the o-cresolphthalein complexone method. Inflammation was assessed by monitoring NF-κB activation using Western blots as well as IL-1ß, IL-6 and TNF-α secretion by ELISAs. Small interfering RNA (siRNA) approaches enabled us to determine which signaling pathways were involved. RESULTS: Indoxyl-sulfate increased OM-induced hVICs osteogenic transition and calcification in a concentration-dependent manner. This effect was blocked by silencing the receptor for IS (the aryl hydrocarbon receptor, AhR). Exposure to IS promoted p65 phosphorylation, the blockade of which inhibited IS-induced mineralization. Exposure to IS promoted IL-6 secretion by hVICs, a phenomenon blocked by silencing AhR or p65. Incubation with an anti-IL-6 antibody neutralized IS's pro-calcific effects. CONCLUSION: IS promotes hVIC mineralization through AhR-dependent activation of the NF-κB pathway and the subsequent release of IL-6. Further research should seek to determine whether targeting inflammatory pathways can reduce the onset and progression of CKD-related CAS.
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Estenose da Valva Aórtica , Calcinose , Humanos , Valva Aórtica/metabolismo , NF-kappa B/metabolismo , Estenose da Valva Aórtica/metabolismo , Interleucina-6/farmacologia , Indicã/farmacologia , Indicã/metabolismo , Osteogênese , Receptores de Hidrocarboneto Arílico/metabolismo , Calcinose/metabolismo , Células Cultivadas , Diferenciação Celular , RNA Interferente Pequeno/metabolismo , Sulfatos/metabolismo , Sulfatos/farmacologiaRESUMO
OBJECTIVE: Angiopoietins (Angs) regulate endothelial permeability. Ang-1 and 2 (Ang-1 and Ang-2) are implied in endothelial stability through an antagonism effect. The objectives of the present study were to describe and compare changes in Ang levels after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). DESIGN: A prospective, single-center study. PARTICIPANTS: Adult patients with aortic stenosis scheduled for SAVR or TAVR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ang-1 and Ang-2 were measured using an enzyme-linked immunosorbent assay right before surgery (T0), at the end of surgery (T1), and at day one (T2). Sixty consecutive patients (SAVR group [nâ¯=â¯30] and TAVR group [nâ¯=â¯30]) were included between January and June 2017. Ang-1 decreased significantly after both TAVR (T0: 3,663 [2,602-4,262]; T1: 1,611 [981-2,409]; T2: 1,082 [652-1,589] ng/mL; p < 0.0001) and SAVR (T0: 1,603 [975-2,849]; T1: 783 [547-1,024]; T2: 828 [460-1,227] ng/mL; pâ¯=â¯0.0001). Ang-2 increased significantly after SAVR (T0: 2,472 [1,502-3,622]; T1: 2,997 [1,759-3,839]; T2: 5,421 [3,557-7,087] ng/mL; p < 0.0001) but did not change markedly after TAVR (T0: 3,343 [2,661-6,272]; T1: 3,788 [2,574-5,016]; T2: 3,446 [3,029-6,313] ng/mL; pâ¯=â¯0.066). Among patients with paravalvular leakage, the changes in the plasma Ang-2 level and the Ang-2/Ang-1 ratio were greater. CONCLUSION: SAVR induces greater alterations of Ang homeostasis than TAVR, confirming a role for the use of cardiopulmonary bypass. Paravalvular leakage after TAVR is associated with Ang changes similar to those observed with SAVR.
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Angiopoietinas/sangue , Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Substituição da Valva Aórtica Transcateter , Adulto , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Humanos , Estudos Prospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Left atrial (LA) enlargement has been previously identified as a predictor of mortality in patients with medically managed mitral regurgitation (MR) due to mitral valve prolapse (MVP). No study has specifically assessed the prognostic value of LA size in patients undergoing mitral valve repair (MVRp). OBJECTIVE: We aimed to investigate the relationship between LA area and mortality in patients in sinus rhythm (SR) undergoing MVRp for MVP. METHODS: We included 305 patients in SR who underwent MVRp for MVP. Median follow-up time was 7.9 years. Patients were divided into 3 groups: LA area ≤25 cm2 (reference group), LA 26-30 cm2, and LA >30 cm2. RESULTS: Compared with patients with an LA area ≤25 cm2, those with an LA area >30 cm2 had a lower 10-year survival (98 ± 2 vs. 86 ± 4%; p = 0.037). In multivariate analysis, after adjustment for established outcome predictors including age, symptoms, EuroSCORE, and left ventricular size and function, LA enlargement >30 cm2 was associated with increased mortality (adjusted HR = 2.20, 95% CI 1.03-4.90; p = 0.042), whereas LA enlargement between 26 and 30 cm2 was not (adjusted HR = 1.37, 95% CI 0.56-3.56; p = 0.52). CONCLUSION: LA enlargement is independently predictive of long-term mortality after MVRp in patients in SR with severe MR due to MVP. Our findings suggest that MVRp should be considered before the LA area exceeds 30 cm2.
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Função do Átrio Esquerdo , Ecocardiografia , Átrios do Coração/patologia , Insuficiência da Valva Mitral/diagnóstico por imagem , Prolapso da Valva Mitral/diagnóstico por imagem , Idoso , Procedimentos Cirúrgicos Cardíacos , Feminino , França/epidemiologia , Átrios do Coração/diagnóstico por imagem , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/mortalidade , Insuficiência da Valva Mitral/cirurgia , Prolapso da Valva Mitral/mortalidade , Prolapso da Valva Mitral/cirurgia , Análise Multivariada , Valor Preditivo dos Testes , Análise de SobrevidaRESUMO
To develop a mathematical formula for calculating the length of ruptured mitral valve chordae (with a view to surgically replacing them with artificial chordae) when rupture occurs at scallop A1, A3, P1, or P3. We studied human cadaver hearts collected by the Faculty of Medicine at Amiens Picardy University Hospital. The donors' mean age standard deviation age at death was 79 ± 10. After weighing and dissection, we counted the number of para-commissural chordae per scallop and measured their length with a digital calliper. A total of 31 human cadaver hearts (14 from females and 17 from males) were analyzed. The mean lengths of scallops A1, A2, A3, P1, P2, and P3 were 17.45, 19.42, 17.58, 13.32, 14.52, and 13.26 mm, respectively. A linear regression gave the following mathematical equations: A1â¯=â¯0.96 × A2- - 1.3 (R: 0.99; P < 0.001); A3â¯=â¯0.9 × A2â¯+â¯0.17 (R: 0.95; P < 0.01); P1â¯=â¯0.87 × P2 +0.74 (R: 0.89; P < 0.001), and P3â¯=â¯0.91 × P2 - 0.01 (R: 0.87; P < 0.0001). When the patient's anatomy prevents manual measurements of the chordae during mitral valve repair surgery, the mathematical formulae derived here can be used to predict the length of the chordae on A1, A3, P1, and P3 from the length of the chordae on A2 and P2. The mitral chordae can therefore be replaced with prostheses with a great degree of precision.
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Procedimentos Cirúrgicos Cardíacos , Insuficiência da Valva Mitral , Masculino , Feminino , Humanos , Valva Mitral/cirurgia , Cordas Tendinosas/cirurgia , Cordas Tendinosas/anatomia & histologia , Insuficiência da Valva Mitral/cirurgia , CadáverRESUMO
Introduction: Cardiac metastasis (CM) is a rare lung cancer location. It often remains clinically silent but may cause life-threatening complications. Better survival rates thanks to the immunotherapy revolution and the improving performance of imaging lead to an increasing number of CM diagnosis. Case Presentation: We report a case of a 54-year-old woman who was diagnosed with a stage IIIa non-small cell lung cancer. She developed a right ventricular CM without symptoms during treatment by immunotherapy after concurrent chemoradiotherapy. Cardiac magnetic resonance imaging confirmed the presence of an endocavitary lesion in the right ventricle apex. Complete surgical resection through a right ventriculotomy was performed. Conclusion: The diagnosis of similar cases has become more frequent due to immunotherapy and more advanced imaging technology. Our case report also highlights the fact that CM surgery has to be considered as a successful therapeutic option in those oligo-progression situations. Guidelines on the management and treatment of lung cancer CM are needed as well as larger studies to evaluate the survival benefit from surgical treatment.
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AIMS: Inflammatory cytokines play a critical role in the progression of calcific aortic valve disease (CAVD), for which there is currently no pharmacological treatment. The aim of this study was to test the hypothesis that interleukin-8 (IL-8), known to be involved in arterial calcification, also promotes aortic valve calcification (AVC) and to evaluate whether pharmacologically blocking the IL-8 receptor, CXC motif chemokine receptor 2 (CXCR2), could be effective in preventing AVC progression. METHODS AND RESULTS: A cohort of 195 patients (median age 73, 74% men) diagnosed with aortic valve stenosis (severe in 16.9% of cases) were prospectively followed by CT for a median time of 2.6 years. A Cox proportional hazards regression analysis indicated that baseline IL-8 serum concentrations were associated with rapid progression of AVC, defined as an annualized change in the calcification score by CT ≥ 110 AU/year, after adjustment for age, gender, bicuspid anatomy, and baseline disease severity. In vitro, exposure of primary human aortic valvular interstitial cells (hVICs) to 15 pg/mL IL-8 induced a two-fold increase in inorganic phosphate (Pi)-induced calcification. IL-8 promoted NFκB pathway activation, MMP-12 expression, and elastin degradation in hVICs exposed to Pi. These effects were prevented by SCH527123, an antagonist of CXCR2. The expression of CXCR2 was confirmed in hVICs and samples of aortic valves isolated from patients with CAVD, in which the receptor was mainly found in calcified areas, along with MMP-12 and a degraded form of elastin. Finally, in a rat model of chronic kidney disease-associated CAVD, SCH527123 treatment (1 mg/kg/day given orally for 11 weeks) limited the decrease in aortic cusp separation, the increase in maximal velocity of the transaortic jet, and the increase in aortic mean pressure gradient measured by echocardiography, effects that were associated with a reduction in hydroxyapatite deposition and MMP-12 expression in the aortic valves. CONCLUSION: Overall, these results highlight, for the first time, a significant role for IL-8 in the progression of CAVD by promoting calcification via a CXCR2- and MMP-12-dependent mechanism that leads to elastin degradation, and identify CXCR2 as a promising therapeutic target for the treatment of CAVD.
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OBJECTIVE: In mitral insufficiency, trans-esophageal echocardiography (TEE) analysis of the mitral valve is an indispensable and irreplaceable examination to establish precisely the type of surgical repair to be performed and the exact length of neo-chordae to be used for an anatomical repair. The aim of our study is to find a predictive model of the Echographic Measurement (EM) variable according to the Manual Measurement (MM) variable of the mitral valve chordae, when the echocardiography measurement is not feasible. PATIENTS AND METHODS: This is a retrospective study on 191 patients undergoing mitral valve repair. The sex ratio (M/F) is 2.13 (130 men and 61 women). The collection of data of mitral chordae measurements performed echographically in preoperatively conditions, and then manually in intraoperatively conditions from January 2008 to December 2016 was made from the medical records of patients at the cardiology and cardiac surgery department of the University Hospital Center of Amiens in Picardy. RESULTS: For this study 191 patients of mean age of 68 ± 13 years were included. The averages of the MM and EM of the mitral chordae were respectively 23 ± 2.5 mm and 24 ± 2.4 mm. The Pearson correlation coefficient was 0.897 (p-value < 10-4) showing a strong positive correlation between MM and EM. The results of the linear regression allow us to found the following mathematical model: EM = 0.87 × MM + 4. CONCLUSIONS: When patients have a contraindication to transesophageal echocardiography or when TEE is not feasible, manual measurement is performed during the surgery. By using the values obtained (MM) in the model, it is possible to predict the corresponding echographic measurements. This allows us to achieve the mitral tendinous chordae substitution with a very high precision. TRIAL REGISTRATION: Retrospectively registered.
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Insuficiência da Valva Mitral , Salas Cirúrgicas , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia , Ecocardiografia Transesofagiana/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Estudos RetrospectivosRESUMO
Background: Conventional transthoracic (TTE) and transoesophageal echocardiography (TEE) parameters assessing right ventricle (RV) systolic function are daily used assuming their clinical interchangeability. RV longitudinal shortening fraction (RV-LSF) is a two-dimensional speckle tracking parameter used to assess RV systolic function. RV-LSF is based on tricuspid annular displacement analysis and could be measured with TTE or TEE. Objective: The aim of the study was to determine if RV-LSFTTE and RV-LSFTEE measurements were interchangeable in the perioperative setting. Methods: Prospective perioperative TTE and TEE echocardiography were performed under general anesthesia during scheduled cardiac surgery in 90 patients. RV-LSF was measured by semi-automatic software. Comparisons were performed using Pearson correlation and Bland-Altman plots. RV-LSF clinical agreement was determined as a range of -5 to 5%. Results: Of the 114 patients who met the inclusion criteria, 90 were included. The mean preoperative RV-LSFTTE was 20.4 ± 4.3 and 21.1 ± 4.1% for RV-LSFTEE. The agreement between RV-LSF measurements was excellent, with a bias at -0.61 and limits of agreement of -4.18 to 2.97 %. All measurements fell within the determined clinical agreement interval in the Bland-Altman plot. Linear regression analysis showed a high correlation between RV-LSFTTE and RV-LSFTEE measurement (r = 0.9; confidence interval [CI] 95%: [0.87-0.94], p < 0.001). Conclusion: RV-LSFTTE and RV-LSFTEE measurements are interchangeable, allowing RV-LSF to be a helpful parameter for assessing perioperative changes in RV systolic function. NCT: NCT05404737. https://www.clinicaltrials.gov/ct2/show/NCT05404737.
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AIMS: Left ventricular (LV) dysfunction is the first cause of late mortality after mitral valve surgery. In this retrospective analysis, we studied the association between preoperative echocardiographic LV measures and occurrence of LV dysfunction after mitral valve repair (MVR). METHODS AND RESULTS: Between 1991 and 2009, 335 consecutive patients underwent MVR for severe mitral regurgitation due to leaflet prolapse in our institution. Echocardiography was performed preoperatively and at 10.8 (9.1-12.0) months after surgery in 303 patients who represented the study population. Cardiac events were recorded during follow-up. LV ejection fraction (EF) decreased from 68 ± 9% before surgery to 59 ± 9% post-operatively (P < 0.001). Preoperative EF <64% and LV end-systolic diameter (ESD) ≥ 37 mm were the best cut-off values for the prediction of post-operative LV dysfunction (EF < 50%). On the basis of a combined analysis, the occurrence of post-operative LV dysfunction was 9% when EF was ≥ 64% and LVESD < 37 mm, 21% with EF < 64% or LVESD ≥ 37 mm, and 33% with EF < 64% and LVESD ≥ 37 mm (P for trend < 0.001). The combined variable EF < 64% and LVESD ≥ 37 mm added incremental prognostic value to the multivariable regression model (P = 0.001). CONCLUSION: Simple preoperative echocardiography measures allow the prediction of LV dysfunction after MVR in patients with leaflet prolapse. Patients with preoperative EF ≥ 64% and LVESD < 37 mm incur relatively low risk of post-operative LV dysfunction.
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Insuficiência da Valva Mitral/cirurgia , Complicações Pós-Operatórias/diagnóstico , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Idoso , Ecocardiografia Doppler , Feminino , Humanos , Modelos Logísticos , Masculino , Insuficiência da Valva Mitral/etiologia , Prolapso da Valva Mitral/complicações , Modelos de Riscos Proporcionais , Curva ROC , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
INTRODUCTION: Cytokine storm and endotoxin release during cardiac surgery with cardiopulmonary bypass (CPB) have been related to vasoplegic shock and organ dysfunction. We hypothesised that early (during CPB) cytokine adsorption with oXiris membrane for patients at high risk of inflammatory syndrome following cardiac surgery may improve microcirculation, endothelial function and outcomes. METHODS AND ANALYSIS: The Oxicard trial is a prospective, monocentric trial, randomising 70 patients scheduled for cardiac surgery. The inclusion criterion is patients aged more than 18 years old undergoing elective cardiac surgery under CPB with an expected CPB time >90 min (double valve replacement or valve replacement plus coronary arterial bypass graft). Patients will be allocated to the intervention group (n=35) or the control group (n=35). In the intervention group, oXiris membrane will be used on the Prismaflex device (Baxter) at blood pump flow of 450 mL/min during cardiac surgery under CPB. In the control group, cardiac surgery under CPB will be conducted as usual without oXiris membrane. An intention-to-treat analysis will be performed. The primary endpoint will be the microcirculatory flow index measured by sublingual microcirculation device at day 1 following cardiac surgery. The secondary endpoints will be other microcirculation variables at CPB end, 6 hours after CPB, at day 1 and at day 2. We also aim to evaluate the occurrence of major cardiovascular and cerebral events (eg, myocardial infarction, stroke, ischaemic mesenteric, resuscitated cardiac arrest, acute kidney injury) within the first 30 days. Cumulative catecholamine use, intensive care unit length of stay, endothelium glycocalyx shedding parameters (syndecan-1, heparan-sulfate and hyaluronic acid), inflammatory cytokines (tumour necrosis factor (TNF) alpha, interleukin 1 (IL1) beta, IL 10, IL 6, lipopolysaccharide, endothelin) and endothelial permeability biomarkers (angiopoietin 1, angiopoietin 2, Tie2 soluble receptor and Vascular Endothelial Growth Factor (VEGF) will also be evaluated. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Institutional Review Board of the University Hospital of Amiens (registration number ID RDB: 2019-A02437-50 in February 2020). Results of the study will be disseminated via peer-reviewed publications and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04201119.
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Procedimentos Cirúrgicos Cardíacos , Ponte Cardiopulmonar , Adolescente , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Humanos , Microcirculação , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator A de Crescimento do Endotélio VascularRESUMO
We report a 62-year-old woman who was scheduled for an elective Tirone David valve sparing aortic root replacement under cardiopulmonary bypass. Within the next few hours, the patient developed bilateral acute ischemia of both lower limbs. A thoracic and abdominopelvic computed tomography scan showed acute Type A aortic dissection with a perforation at the brachiocephalic arterial trunk and a complete malperfusion of the inferior mesenteric and iliac arteries.
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PURPOSE: Data on the benefit or or harmful effects of oxygen level on ischemic reperfusion injuries in cardiac surgery are insufficient. We hypothesized that hyperoxia during cardiopulmonary bypass decreases the incidence of postoperative atrial fibrillation (POAF) and ventricular fibrillation, and therefore decreases cardiovascular morbidity (CARDIOX study). METHODS: An open-label, randomized clinical trial including adults undergoing elective cardiac surgery, i.e. cardiopulmonary bypass (CPB) randomized 1:1 to an intervention group or standard group at two French University Hospitals from June 2016 to October 2018. The intervention consisted in delivering of an inspired fraction of oxygen of one to one during CPB. The standard care consisted in delivering oxygen to achieve a partial arterial blood pressure less than 150 mmHg. The primary endpoint was the occurrence of POAF and/or ventricular tachycardia/ventricular fibrillation (VT/VF) within the 15 days following cardiac surgery. The secondary endpoint was the occurrence of major adverse cardiovascular events (MACCE: in-hospital mortality, stroke, cardiac arrest, acute kidney injury, and mesenteric ischemia). RESULTS: 330 patients were randomly assigned to either the intervention group (n = 161) or the standard group (n = 163). Mean PaO2 was 447 ± 98 mmHg and 161 ± 60 mmHg during CPB, for the intervention and standard group (p < 0.0001) respectively. The incidence of POAF or VT/VF were similar in the intervention group and the standard group (30% [49 of 161 patients] and 30% [49 of 163 patients], absolute risk reduction 0.4%; 95% CI, - 9.6-10.4; p = 0.94). MACCE was similar between groups with, an occurrence of 24% and 21% for the intervention group and the standard groups (absolute risk reduction 3.4%; 95% CI, - 5.7-12.5; p = 0.47) respectively. After adjustment, the primary and secondary endpoints remained similar for both groups. CONCLUSION: Hyperoxia did not decrease POAF and cardiovascular morbidity following cardiac surgery with CPB. CLINICALTRIAL. GOV IDENTIFIER: NCT02819739.
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Ponte Cardiopulmonar/normas , Doenças Cardiovasculares/etiologia , Hiperóxia/complicações , Idoso , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/métodos , Ponte Cardiopulmonar/estatística & dados numéricos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/cirurgia , Feminino , França/epidemiologia , Humanos , Hiperóxia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Oxigênio/uso terapêutico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Período Pós-OperatórioRESUMO
BACKGROUND: Various techniques have been proposed for cerebral protection during the surgical treatment of complex aortic disease. The authors propose a revisited strategy of normothermic replacement of the aortic arch to avoid limitations and complications of profound hypothermic circulatory arrest. MATERIALS AND METHODS: From April 2000 to May 2006, 19 patients with an aneurysm of the aortic arch and 10 patients with an acute (7) or a chronic (3) aortic dissection underwent a totally normothermic, complete replacement of the aortic arch using three pumps: One pump ensured antegrade cerebral perfusion, at a flow rate adapted to obtain a pressure of 70 mmHg in the right radial artery, and required a selective cannulation of the supra-aortic vessels. A second pump ensured body perfusion at a flow rate adapted to obtain a pressure of 55 mmHg in the left femoral artery and was situated between the right femoral artery and the right atrium. A special balloon aortic occlusion catheter was placed in the descending thoracic aorta. A third pump ensured intermittent normothermic myocardial perfusion via the coronary venous sinus. The arch reconstruction was performed with no time limit. RESULTS: There were two operative, in-hospital (6.8%) mortalities. All others patients were rapidly extubated, except one, with no neurological sequelae, and postoperative course was uneventful, without coagulopathy or hepato-renal impairment. CONCLUSIONS: In the light of these results, a normothermic procedure is possible for arch surgery and may ensure a more physiological autoregulation of cerebral blood flow while maintaining body perfusion without high vascular resistances.
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Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Perfusão/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ponte Cardiopulmonar/métodos , Circulação Cerebrovascular/fisiologia , Artéria Femoral/cirurgia , Átrios do Coração/cirurgia , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Artéria Radial/cirurgia , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/métodosRESUMO
BACKGROUND AND OBJECTIVES: Zeta-associated protein 70 (ZAP-70), a member of the Syk family of protein tyrosine kinases, is normally expressed in T and NK cells. While little is known about ZAP-70 expression in normal human B cells, it has been reported that ZAP-70 is expressed in a subset of patients with chronic lymphocytic leukemia (CLL) with a poor prognosis. In this study, we examined the expression and phosphorylation status of ZAP-70 in B-lineage acute lymphoblastic leukemia (Blin-ALL). DESIGN AND METHODS: First, ZAP-70 protein expression was assessed by Western blotting and flow cytometry and ZAP-70 mRNA transcripts were analyzed by reverse transcription polymerase chain reaction (RT-PCR) on human precursor B cell lines. Experiments were then carried out on cells obtained from 18 patients with Blin-ALL and from normal human bone marrow. RESULTS: ZAP-70 was constitutively expressed and phosphorylated on tyr319 in human precursor Blin-ALL cell lines as well as in primary B leukemic cells from all examined Blin-ALL patients with pro-B, pre-B and B phenotypes, but not in malignant myeloid cells. Importantly, analysis of normal human bone marrow revealed expression of ZAP-70 transcripts only in the CD34+ cell fraction (either CD19-CD10- or CD19+CD10+) but not in the CD34- cell fraction (CD19+sIgM- pre-B cells or CD19+sIgM+ immature B cells). INTERPRETATION AND CONCLUSIONS: ZAP-70 was found to be expressed in the CD34+ normal bone marrow compartment including earlier B-cell progenitors, but not in CD34- pre-B and immature B cells. By contrast, ZAP-70 was consistently expressed and phosphorylated in Blin-ALL cells. Further studies are required to determine whether ZAP-70 may play a pathophysiological role in Blin-ALL.
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Linfoma de Burkitt/genética , Linfoma de Burkitt/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteína-Tirosina Quinase ZAP-70/biossíntese , Proteína-Tirosina Quinase ZAP-70/genética , Adulto , Antígenos CD34/biossíntese , Medula Óssea/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , FosforilaçãoRESUMO
The aim of the study was to assess the impact of atrial fibrillation (AF) on outcome in patients who underwent mitral valve repair (MVRp) for mitral valve prolapse (MVP). Four hundred and forty-three consecutive patients underwent MVRp for organic mitral regurgitation due to MVP. Echocardiography was performed preoperatively and after surgery. Postoperative left ventricular dysfunction (LVD) was defined as left ventricular ejection fraction (LVEF) <50%. Before surgery, 187 patients (42%) had preoperative AF. After surgery, LVEF significantly decreased from 67 ± 9% to 56 ± 10% (p <0.0001). Compared with patients in sinus rhythm (SR), those in AF were significantly older (p <0.0001), had more severe symptoms (p = 0.004), had lower LVEF (p = 0.002), and higher EuroSCORE (p = 0.05). Compared with patients in SR, patients with AF had significantly lower 10-year survival (64 ± 4% vs 83 ± 3%, p = 0.001). On multivariate analysis, preoperative AF was identified as an independent predictor of overall mortality (hazard ratio 1.67; 95% confidence interval 1.15 to 2.42; p = 0.007). At 10 years, patients with paroxysmal AF had lower survival and higher heart failure rate than patients in SR (78 ± 3% vs 66 ± 6%) but had a better outcome compared with those with permanent AF (66 ± 6% vs 53 ± 6%, p = 0.022). Patients with AF had a significantly higher rate of postoperative LVD (23.3% vs 13.4%, p = 0.007). In conclusion, preoperative AF is a predictor of long-term mortality and postoperative LVD after MVRp for MVP. To improve postoperative outcome, surgery in these patients should be performed before onset of AF.
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Fibrilação Atrial/complicações , Implante de Prótese de Valva Cardíaca , Prolapso da Valva Mitral/complicações , Disfunção Ventricular Esquerda/etiologia , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Ecocardiografia , Eletrocardiografia , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prolapso da Valva Mitral/diagnóstico por imagem , Prolapso da Valva Mitral/cirurgia , Período Pós-Operatório , Período Pré-Operatório , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
The authors propose a new strategy of normothermic perfusion for replacement of the aortic arch to avoid the complications of profound hypothermic circulatory arrest. Six patients underwent complete replacement of the aortic arch under normothermia using two pumps for the body (one for the brain and the thoracoabdominal aortic branches) and one for the heart. The surgical procedure was performed with no time limit. There were no operative or late deaths. No patients had neurologic deficit and all were rapidly extubated with uneventful postoperative courses. The method preserves autoregulation of cerebral blood flow and maintains body perfusion without high vascular resistances.
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Aorta Torácica/cirurgia , Implante de Prótese Vascular , Ponte Cardiopulmonar/métodos , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , TemperaturaRESUMO
BACKGROUND AND AIMS OF THE STUDY: Manual decalcification of the aortic valve was performed systematically in a prospective series of patients with asymptomatic moderate aortic stenosis (AS) undergoing coronary artery bypass grafting (CABG). This study addressed two main issues: (i) whether aortic valve decalcification is a good option to relieve moderate AS; and (ii) whether the natural progression of AS may be delayed by manual valve debridement when surgery is indicated for coronary disease. METHODS: Between October 1997 and March 2001, 14 adult patients with moderate AS underwent concomitant surgical repair of the aortic valve during CABG. Manual valve debridement with restoration of cusp mobility was attempted. Calcified deposits were removed by careful dissection. All patients underwent myocardial revascularization; a mean of 2.38 grafts was performed per patient. RESULTS: Immediately after surgery, mean aortic valve area index (AVAI) was improved, from 0.56+/-0.12 to 1.43+/-0.25 cm2/m2. Patients with the slowest recalcification rates were those with a postoperative/preoperative AVAI ratio of 1.6 to 2.4, those in whom the degree of postoperative aortic insufficiency was very similar to the degree of preoperative regurgitation, and those in whom the preoperative AVAI was >0.55 cm2/m2. CONCLUSION: Manual aortic valve debridement for moderate AS is a good option when surgery must be performed for coronary disease; the best results were obtained in patients with senile stenosis of a tricuspid aortic valve with an AVAI of 0.55-0.9 cm2/m2.
Assuntos
Estenose da Valva Aórtica/cirurgia , Ponte de Artéria Coronária , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Angiografia Coronária , Reestenose Coronária/etiologia , Progressão da Doença , Ecocardiografia Transesofagiana , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
A case of purulent pericarditis with an unusual aetiology and a favourable outcome is reported. This patient presented with purulent pericarditis secondary to an oesophago-pericardial fistula caused by a squamous carcinoma of the oesophagus. A review of the literature revealed only a small number of similar cases. The prognosis can be improved by rapid diagnosis, appropriate antibiotic therapy, surgical drainage and surgical repair of the fistula. An aggressive therapeutic approach should be proposed in order to achieve long-term remission in these frequently young patients.